Parkinson disease is one of the most widespread neurological disorders accompanied by movement disorders, caused mainly by the loss of dopamine-containing cells of the nigrastrial pathway. The prevalence of Parkinson disease is 1% of adult population under 60 years of age, 5-10%—in population of 60-80 years of age [1]. Parkinson disease requires prolonged treatment, sometimes during the whole life, and requires combining different drugs, usually dopamine system agonists and anticholinetics.
Different drugs are used in Parkinson disease treatment. The most used are drugs containing L-DOPA—a dopamine precursor (levodopa, carbidopa, nakom). These drugs are used as substitution therapy, because the disease is associated with the reduction of dopamine level. Other drugs are used: drugs suppressing the stimulating action of cortical glutamate receptors, which develops on the background of dopamine level reduction (midantan); dopamine (peripheral) receptors agonists (ropinirole); MAO-B inhibitors (selegiline) and central anticholinetics.
The main drug of antiparkinson therapy, effectively eliminating the disease symptoms, is levodopa. Antiparkinson action of levodopa is caused by its transformation into dopamine in the CNS. However, only 1-3% of the administered drug reach the target (brain) so levodopa is usually combined with peripheral DOPA-carboxylase inhibitors (carbidopa, etc.), raising the percentage of levodopa reaching the brain up to 10% [2].
The drawback of levodopa-containing drugs are [1, 2]: 1) low effectiveness (the drug is highly effective in ⅓ of patients and less effective in another ⅓, the rest of patients are intolerant to the drug or do not experience its positive effects at all); 2) many adverse effects (anorexia, vomiting, tachycardia, dyskinesia, appearing in almost 80% of patient, mental disorders, etc.); 3) movement fluctuations (“on-off” syndrome); 4) drug tolerance—after 3-4 years of levodopa therapy its efficiency often decreases, up to total inefficiency, independent of the patient's condition in the beginning of treatment, so the treatment of moderate parkinsonism is avoided until the disease starts to affect the patient's normal life significantly; however, it is shown [2], that early start of treatment reduces mortality associated with Parkinson disease.
To reduce the required dose and adverse effects levodopa is usually combined with other drugs, but they do not eliminate the aforementioned drawbacks completely [1, 2], and these drugs are insufficiently effective without levodopa.
As for the drugs having potentiating effect on dopaminergic system, the presence of such effect is insufficient to prove that the compound can significantly affect dopaminergic system without L-DOPA and have antiparkinson activity.
Due to these factors, the search and creation of new low-toxic antiparkinson drugs continues to be relevant in the present time.